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KMID : 0379520080240010001
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한국독성학회지
2008 Volume.24 No. 1 p.1 ~ p.9
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Phosphoinositides Signaling and Epithelial-to-Mesenchymal Transition
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Lee Chang-Ho
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Abstract
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PtdIns(4,5)P₂ is a key cellular phosphoinositide that localizes in separate and distinctive pools in subcellular membrane and vesicular compartments. In membranes, PtdIns(4,5)P₂ acts as a precursor to second messengers and is itself a main signaling and targeting molecule. Specific subcellular localization of type I PIP kinases directed by interacting with specific targeting module differentiates PtdIns(4,5)P₂ production in a spatial and temporal manner. Several lines of evidences support the idea that PtdIns(4,5)P₂ is generated in very specific pools in a spatial and temporal manner or by feeding PtdIns(4,5)P₂ directly to effectors. In this concept, the interaction of PIPKI isoforms with a specific targeting module to allow precise subcellular targeting modulates highly specific PtdIns(4,5)P₂ synthesis and channeling overall effectors. For instance, localization of PIPKIγ661 to focal adhesions by an interaction with talin results in spatial and temporal production of PtdIns(4,5)P₂, which regulates EGF-stimulated directional cell migration. In addition, Type Iγ PIPK is targeted to E-cadherin in cell adherence junction and plays a role in controlling dynamics of cell adherence junction and endocytosis of E-cadherin. Characterizing how PIP kinase isoforms are regulated by interactions with their targeting modules, as well as the mechanisms by which their product, PtdIns(4,5)P₂, exerts its effects on cellular signaling processes, is crucial to understand the harmonized control of numerous cellular signaling pathways. Thus, in this review the roles of the PtdIns(4)P(5) kinases and PtdIns(4,5)P₂ were described and critically reviewed in terms of regulation of the E-cadherin trafficking, cell migration, and formation of cell adherence junction which is indispensable and is tightly controlled in epithelial-to-mesenchymal transition process.
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KEYWORD
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PIP kinases, PIPKIγ661, E-cadherin, EMT, Adherence Junction
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